The medical value of detecting circulating tumor cells (CTCs) in peripheral blood is now established, and a specific approach has FDA approval for managing metastatic patients. While the value is clear, it is also limited in application. For example, the reported results are uninformative for a large percentage of metastatic patients, and no validation exists for earlier stages. The cancer bioengineering research partnership (CBRP) proposes to develop a technology for CTC detection that overcomes these limitations. We will develop a new instrument, the Fiber Array Scan Technology (FAST) cytometer that efficiently scans the large numbers of cells required to detect CTCs and a cell preparation protocol that is optimized for cell retention. We will use these developments to investigate whether more metastatic patients have CTCs than current approaches indicate. We will also investigate the medical efficacy of CTC detection in early stage cancer patients. In addition we will investigate applications for staging at diagnosis, as well as for longitudinal therapy monitoring and long-term patient management. The effort integrates clinical oncology with biophysical analysis methods and opto-mechanical engineering. The CBRP will develop a rare cell detection system that can analyze approximately 50 million cells in 2 minutes with a sensitivity of 10% false negatives and a false positive ratio of less than 1 in 107. The Lead Investigators of the CBRP have developed the initial proof of concept through a multidisciplinary approach bridging optical design, statistical software analysis, experimental medicine, oncology, and pathology at the leading institutions, the Palo Alto Research Center (PARC) and The Scripps Research Institute (TSRI), as well as at the participating institutions, Scripps Clinic and the Scripps Cancer Center. The lead investigators are Richard Bruce, Ph.D. (PARC), who is the principal investigator and will in addition lead the optical and system engineering efforts; Peter Kuhn, Ph.D. (TSRI), who will lead the experimental processing; and Jorge Nieva, MD (TSRI and Scripps Cancer Center), who will lead the oncology and pathology of the CBRP. The lead investigators are experts in their respective fields and provide the required expertise for the multi-disciplinary research program of the CBRP. [unreadable] [unreadable] [unreadable]